Gut microbiota interspecies interactions shape the response of Clostridioides difficile to clinically relevant antibiotics.
Gut microbiota interspecies interactions shape the response of Clostridioides difficile to clinically relevant antibiotics.
复制标题
DOI：
10.1371/journal.pbio.3002100
复制
发表时间：
2023-05
期刊：
影响因子：
9.8
通讯作者：
中科院分区：
文献类型：
--
作者：
在人类肠道中，病原体艰难梭菌的生长受到与人类肠道微生物群成员的种间相互作用的复杂网络的影响。我们使用人类肠道群落的自下而上组装来研究种间相互作用对艰难梭菌对临床相关抗生素的抗生素反应的贡献。我们确定了两类改变艰难梭菌抗生素敏感性的微生物相互作用：导致艰难梭菌在高抗生素浓度下生长能力增强的相互作用（罕见）和导致艰难梭菌在低抗生素浓度下生长增强的相互作用（常见）。基于全基因组转录分析数据，我们证明，流行的肠道物种脱硫弧菌猪产生的硫化氢导致的金属螯合增加了甲硝唑对艰难梭菌的最低抑制浓度 (MIC)。与对抗生素比艰难梭菌更敏感的物种竞争，由于竞争性释放，导致艰难梭菌在低抗生素浓度下生长增强。动态计算模型确定了驱动这种效应的生态原理。我们的结果提供了对影响艰难梭菌对抗生素反应的生态和分子原理的更深入的了解，这可以为治疗干预措施提供信息。这项研究探讨了人类肠道微生物群组成成员之间的相互作用如何影响病原体艰难梭菌对临床相关抗生素的反应，为影响这一健康相关系统中抗生素敏感性的生态原理和分子机制提供了重要见解。
In the human gut, the growth of the pathogen Clostridioides difficile is impacted by a complex web of interspecies interactions with members of human gut microbiota. We investigate the contribution of interspecies interactions on the antibiotic response of C. difficile to clinically relevant antibiotics using bottom-up assembly of human gut communities. We identify 2 classes of microbial interactions that alter C. difficile’s antibiotic susceptibility: interactions resulting in increased ability of C. difficile to grow at high antibiotic concentrations (rare) and interactions resulting in C. difficile growth enhancement at low antibiotic concentrations (common). Based on genome-wide transcriptional profiling data, we demonstrate that metal sequestration due to hydrogen sulfide production by the prevalent gut species Desulfovibrio piger increases the minimum inhibitory concentration (MIC) of metronidazole for C. difficile. Competition with species that display higher sensitivity to the antibiotic than C. difficile leads to enhanced growth of C. difficile at low antibiotic concentrations due to competitive release. A dynamic computational model identifies the ecological principles driving this effect. Our results provide a deeper understanding of ecological and molecular principles shaping C. difficile’s response to antibiotics, which could inform therapeutic interventions. This study examines how interactions between constituent members of the human gut microbiome influence the pathogen C. difficile’s response to clinically relevant antibiotics, providing key insights into ecological principles and molecular mechanisms that influence antibiotic susceptibility in this health-relevant system.
登录
查看更多内容
细菌群落抗菌素耐药性的生态学和进化。
DOI：
10.1038/s41396-020-00832-7
发表时间：
2021-04
期刊：
The ISME journal
影响因子：
--
作者：
Bottery MJ;Pitchford JW;Friman VP
通讯作者：
Friman VP
影响因子：
3.7
作者：
Dalton T;Dowd SE;Wolcott RD;Sun Y;Watters C;Griswold JA;Rumbaugh KP
通讯作者：
Rumbaugh KP
影响因子：
3.7
作者：
Chong PM;Lynch T;McCorrister S;Kibsey P;Miller M;Gravel D;Westmacott GR;Mulvey MR;Canadian Nosocomial Infection Surveillance Program (CNISP)
通讯作者：
Canadian Nosocomial Infection Surveillance Program (CNISP)
DOI：
10.1038/nri3535
发表时间：
2013-11
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.9
作者：
Deshpande, Aditi;Wu, Xiaoqian;Hurdle, Julian G.
通讯作者：
Hurdle, Julian G.